Comparative study of the presence of Trypanosoma cruzi kDNA, inflammation and denervation in chagasic patients with and without megaesophagus

Abstract

Neuronal lesions have been considered the hallmark of chagasic megaesophagus, but the role of Trypanosoma cruzi and the participation of the inflammatory cells in this process are still debated. In the present study we counted neurons in the oesophagus from patients with and without megaesophagus and further examined these samples for the presence of parasite kDNA and cells with cytolytic potential (Natural Killer cells, cytotoxic lymphocytes and macrophages). The presence of parasite kDNA was demonstrated in 100% of cases with megaesophagus and in 60% of patients without megaesophagus. When analysed for the number of neurons, the patients without megaesophagus could be classified into 2 groups, as having normal or a decreased number of neurons. The former group did not show any inflammatory process, but interestingly, all patients without megaesophagus presenting decreased number of neurons also presented both parasite kDNA and inflammatory process in the organ. We further observed that the numbers of cytotoxic cells in the myenteric plexus region inversely correlate with the number of neurons. These data together strongly suggest that chronic lesions in chagasic megaesophagus might be a consequence of immune-mediated mechanisms, that last until the chronic phase of infection, and are dependent on the persistence of parasite in the host's tissue.

Glial fibrillary acidic protein and S-100 colocalization in the enteroglial cells in dilated and nondilated portions of colon from chagasic patients

“…It was postulated that the immune response to the parasite and consequent parasitism are of crucial importance for the neuronal destruction in the acute phase that continues during the chronic phase and causes organ denervation. Although autoimmunity may also play an important role in the pathogenesis of Chagas' disease, several studies have suggested a positive association among tissue parasitism, inflammation, and severity of the lesions induced by T cruzi [5,7]. The presence of the parasite could explain why the inflammatory processes and the neuronal destruction occur only in a restricted region of the colon, and this was previously demonstrated during the chronic phase by the use of molecular techniques [8,9,22].…”

“…Abnormalities of the enteric nervous system (ENS), namely, degeneration and neuronal number reduction, seem to be essential elements in the pathogenesis of the gastrointestinal disorders [3,5,6]. Actually, it is thought that neuronal loss occurs because of immune cytotoxic mechanisms [6,7] and parasiteinduced lesions [7][8][9]. Ultramicroscopic studies of colon from acutely infected patients have demonstrated that T cruzi penetrates a variety of cells such as macrophages, neurons, and enteric glia cells (EGCs).…”

Doença de Chagas: os 100 anos da descoberta e a atualidade do pensamento do seu descobridor

“…Recentemente, uma sequência de trabalhos, bem conduzidos e cientificamente embasados, alguns deles elaborados por pesquisadores brasileiros em parceria com o eminente Prof. John Furness, da Austrália, trouxe novas contribuições ao entendimento da fisiopatologia da forma digestiva da doença de Chagas. Ficou bem estabelecido que a imunidade e a inflamação crônica persistente têm papel importante na evolução do megaesôfago e que fenômenos de neuroplasticidade fazem parte da fisiopatologia da doença (19,20) . Outra linha de pesquisa que se abriu nas últimas duas décadas foi a do estudo da relação entre megaesôfago e aumento de risco de câncer e da redução de incidência desta doença no megacólon (10,12) .…”

Nitrergic Myenteric Neurons are Spared in Experimental Chagasic Megacolon

“…In patients suffering from Chagasic megacolon for many years, some ganglionic neurons are preserved intact while others are destructed which indicate that certain components of the ENS should be selectively undamaged, and also, implicates in the focal nature of the enteric plexus in this disease [8]. Indeed, recently we described focal accompaniment of the neuronal ganglia in the myenteric plexus of a murine model of long-term T. cruzi infection which reproduces chagasic megacolon [9].…”